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1.
Int J Clin Pract ; 70(8): 657-67, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27384031

RESUMEN

AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina Aspart/administración & dosificación , Insulina de Acción Prolongada/administración & dosificación , Glucemia , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Esquema de Medicación , Sustitución de Medicamentos , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacología , Insulina Aspart/efectos adversos , Insulina Aspart/farmacología , Insulina de Acción Prolongada/efectos adversos , Insulina de Acción Prolongada/farmacología , Resultado del Tratamiento
2.
J Dent Res ; 95(9): 1026-33, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27129490

RESUMEN

Periodontal ligaments (PDLs) play an important role in remodeling the alveolar bond and cementum. Characterization of the periodontal tissue transcriptome remains incomplete, and an improved understanding of PDL features could aid in developing new regenerative therapies. Here, we aimed to generate and analyze a large human PDL transcriptome. We obtained PDLs from orthodontic treatment patients, isolated the RNA, and used a vector-capping method to make a complementary DNA library from >20,000 clones. Our results revealed that 58% of the sequences were full length. Furthermore, our analysis showed that genes expressed at the highest frequencies included those for collagen type I, collagen type III, and proteases. We also found 5 genes whose expressions have not been previously reported in human PDL. To access which of the highly expressed genes might be important for PDL cell differentiation, we used real-time polymerase chain reaction to measure their expression in differentiating cells. Among the genes tested, the cysteine protease cathepsin K had the highest upregulation, so we measured its relative expression in several tissues, as well as in osteoclasts, which are known to express high levels of cathepsin K. Our results revealed that PDL cells express cathepsin K at similar levels as osteoclasts, which are both expressed at higher levels than those of the other tissues tested. We also measured cathepsin K protein expression and enzyme activity during cell differentiation and found that both increased during this process. Immunocytochemistry experiments revealed that cathepsin K localizes to the interior of lysosomes. Last, we examined the effect of inhibiting cathepsin K during cell differentiation and found that cathepsin K inhibition stimulated calcified nodule formation and increased the levels of collagen type I and osteocalcin gene expression. Based on these results, cathepsin K seems to regulate collagen fiber accumulation during human PDL cell differentiation into hard tissue-forming cells.


Asunto(s)
Catepsina K/metabolismo , Ligamento Periodontal/metabolismo , Western Blotting , Diferenciación Celular/genética , Células Cultivadas , Humanos , Ligamento Periodontal/citología , Ligamento Periodontal/crecimiento & desarrollo , ARN/genética , ARN/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma
3.
J Dent Res ; 94(12): 1706-14, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26399972

RESUMEN

Periodontal ligament-associated protein 1 (PLAP-1)/asporin is an extracellular matrix protein preferentially expressed in periodontal ligaments. PLAP-1/asporin inhibits the cytodifferentiation and mineralization of periodontal ligament cells and has important roles in the maintenance of periodontal tissue homeostasis. However, the involvement of PLAP-1/asporin in inflammatory responses during periodontitis is poorly understood. This study hypothesized that PLAP-1/asporin might affect the pathogenesis of periodontitis by regulating periodontopathic bacteria-induced inflammatory responses. Proinflammatory cytokine expression induced by Toll-like receptor 2 (TLR2) and TLR4 was significantly downregulated when PLAP-1/asporin was overexpressed in periodontal ligament cells. Similarly, recombinant PLAP-1/asporin inhibited TLR2- and TLR4-induced proinflammatory cytokine expression in macrophages. We also confirmed that NF-κB activity induced by TLR2 and TLR4 signaling was suppressed by the addition of recombinant PLAP-1/asporin. Furthermore, IκB kinase α degradation induced by TLR4 was reduced by PLAP-1/asporin. Immunoprecipitation assays demonstrated the binding abilities of PLAP-1/asporin to both TLR2 and TLR4. Taken together, PLAP-1/asporin negatively regulates TLR2- and TLR4-induced inflammatory responses through direct molecular interactions. These findings indicate that PLAP-1/asporin has a defensive role in periodontitis lesions by suppressing pathophysiologic TLR signaling and that the modulating effects of PLAP-1/asporin might be useful for periodontal treatments.


Asunto(s)
Proteínas de la Matriz Extracelular/fisiología , Inflamación/fisiopatología , Receptor Toll-Like 2/fisiología , Receptor Toll-Like 4/fisiología , Animales , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Células HEK293 , Humanos , Quinasa I-kappa B/metabolismo , Inmunoprecipitación , Ratones , FN-kappa B/fisiología , Periodontitis/fisiopatología , Periodoncio/inmunología , Periodoncio/fisiología , Reacción en Cadena de la Polimerasa , Células RAW 264.7
4.
J Dent Res ; 94(10): 1417-24, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26239644

RESUMEN

PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor ß activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.


Asunto(s)
Proteínas de la Matriz Extracelular/fisiología , Factores de Crecimiento de Fibroblastos/fisiología , Animales , Western Blotting , Diferenciación Celular/fisiología , Fibroblastos/fisiología , Ratones , Ratones Noqueados , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/fisiología
5.
J Dent Res ; 93(9): 891-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25012810

RESUMEN

Periostin is a mesenchymal cell marker predominantly expressed in collagen-rich fibrous connective tissues, including heart valves, tendons, perichondrium, periosteum, and periodontal ligament (PDL). Knockdown of periostin expression in mice results in early-onset periodontitis and failure of cardiac healing after acute myocardial infarction, suggesting that periostin is essential for connective tissue homeostasis and regeneration. However, its role(s) in periodontal tissues has not yet been fully defined. In this study, we describe a novel human isoform of periostin (PDL-POSTN). Isoform-specific analysis by reverse-transcription polymerase chain-reaction (RT-PCR) revealed that PDL-POSTN was predominantly expressed in the PDL, with much lower expression in other tissues and organs. A PDL cell line transfected with PDL-POSTN showed enhanced alkaline phosphatase (ALPase) activity and calcified nodule formation, compared with cells transfected with the full-length periostin isoform. A neutralizing antibody against integrin-αv inhibited both ALPase activity and calcified nodule formation in cells transfected with PDL-POSTN. Furthermore, co-immunoprecipitation assays revealed that PDL-POSTN bound to integrin αvß3 more strongly than the common isoform of periostin, resulting in strong activation of the integrin αvß3-focal adhesion kinase (FAK) signaling pathway. These results suggest that PDL-POSTN positively regulates cytodifferentiation and mineralization in PDL cells through integrin αvß3.


Asunto(s)
Moléculas de Adhesión Celular/análisis , Ligamento Periodontal/metabolismo , Fosfatasa Alcalina/análisis , Animales , Calcificación Fisiológica/fisiología , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/fisiología , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Línea Celular , Quinasa 1 de Adhesión Focal/metabolismo , Vectores Genéticos/genética , Humanos , Integrina alfaV/fisiología , Integrina alfaVbeta3/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Ligamento Periodontal/citología , Plásmidos/genética , Isoformas de Proteínas/análisis , Isoformas de Proteínas/fisiología , ARN Interferente Pequeño/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiología , Transfección
6.
J Dent Res ; 93(4): 400-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24453179

RESUMEN

PLAP-1/asporin is an extracellular matrix protein that is predominantly expressed in the human periodontal ligament (PDL) and has an aspartic acid (D) repeat polymorphism in its N-terminal region. In this study, we hypothesized that the D repeat polymorphism of PLAP-1/asporin may affect the physiological functions of periodontal ligaments. We established periodontal ligament cell lines transfected with the D13- or D14-PLAP-1 gene. Alkaline phosphatase staining and alizarin red staining revealed that the cytodifferentiation of the D14-PLAP-1-expressing PDL cells was more repressed compared with that of the D13-PLAP-1-expressing cells. Furthermore, the D14-PLAP-1-expressing cells inhibited BMP-2-induced cytodifferentiation more strongly than did the D13-PLAP-1-expressing cells. Western blotting analysis and luciferase assay revealed that D14-PLAP-1 suppressed BMP-2 signal transduction more efficiently than did D13-PLAP-1, and co-immunoprecipitation demonstrated the stronger affinity of the D14-PLAP-1 protein to BMP-2 compared with the D13-PLAP-1 protein. Analysis of these data suggests that the D repeat polymorphism of PLAP-1/asporin has a significant influence on the functions of PDL cells.


Asunto(s)
Proteínas de la Matriz Extracelular/genética , Ligamento Periodontal/metabolismo , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/genética , Antraquinonas , Ácido Aspártico/genética , Proteína Morfogenética Ósea 2/farmacología , Calcificación Fisiológica/genética , Diferenciación Celular/genética , Colorantes , Medios de Cultivo Condicionados , Células HEK293 , Humanos , Proteína 1 Inhibidora de la Diferenciación/análisis , Ligamento Periodontal/citología , Plásmidos , Polimorfismo Genético/genética , Secuencias Repetitivas de Aminoácido/genética , Transducción de Señal/genética , Secuencias Repetidas Terminales/genética , Transfección
7.
J Periodontal Res ; 49(2): 260-7, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23710667

RESUMEN

BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is vital to maintaining the homeostasis of the tooth and periodontal tissue. The influence of iron levels on the cytodifferentiation of PDL cells has not been studied, despite evidence that iron overload or deficiency can have adverse effects on alveolar bone density. The purpose of this study was to examine the effects of altered iron levels on cytodifferentiation in human PDL cells. MATERIAL AND METHODS: Human PDL cells were incubated with culture media supplemented with 10-50 µm ammonium ferric citrate or 5 µm deferoxamine (an iron chelator) during differentiation. Intracellular iron status was assessed by measuring changes in the expression of ferritin RNA and protein. PDL cell differentiation and function were evaluated by measuring osteoblast differentiation gene markers and the capacity of cultures to form mineralized nodules. RESULTS: Iron accumulation resulted in upregulation of light and heavy chain ferritin proteins. Concurrently, osteoblast differentiation gene markers and mineralized nodule formation were suppressed. Iron deficiency resulted in downregulation of light and heavy chain ferritin proteins, suppression of alkaline phosphatase activity and formation of mineralized nodules during PDL cell differentiation. CONCLUSION: We conclude that iron is critical for normal cell differentiation of human PDL cells.


Asunto(s)
Hierro/fisiología , Ligamento Periodontal/citología , Fosfatasa Alcalina/efectos de los fármacos , Animales , Apoferritinas/efectos de los fármacos , Calcificación Fisiológica/efectos de los fármacos , Técnicas de Cultivo de Célula , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Línea Celular , Células Cultivadas , Medios de Cultivo , Deferoxamina/farmacología , Relación Dosis-Respuesta a Droga , Compuestos Férricos/farmacología , Ferritinas/análisis , Marcadores Genéticos/efectos de los fármacos , Humanos , Hierro/farmacología , Quelantes del Hierro/farmacología , Ratones , Osteoblastos/efectos de los fármacos , Ligamento Periodontal/efectos de los fármacos
8.
Anim Genet ; 43(6): 721-9, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22509953

RESUMEN

Respiratory disease is the most important health concern for the swine industry. Genetic improvement for disease resistance is challenging because of the difficulty in obtaining good phenotypes related with disease resistance; however, identification of genes or markers associated with disease resistance can help in the genetic improvement of pig health. The purpose of our study was to investigate whether quantitative trait loci (QTL) associated with disease resistance were segregated in a purebred population of Landrace pigs that had been selected for meat production traits and mycoplasmal pneumonia of swine (MPS) scores over five generations. We analysed 1395 pigs from the base to the fifth generation of this population. Two respiratory disease traits [MPS scores and atrophic rhinitis (AR) scores] and 11 immune-capacity traits were measured in 630-1332 animals at 7 weeks of age and when the animal's body weight reached 105 kg. Each of the pigs, except sires in the base population, was genotyped using 109 microsatellite markers, and then, QTL analysis of the full-sib family population with a multi-generational pedigree structure was performed. Variance component analysis was used to detect QTL associated with MPS or AR scores, and the logarithm of odds (LOD) score and genotypic heritability of the QTL were estimated. Five significant (LOD > 2.51) and 18 suggestive (LOD > 1.35) QTL for respiratory disease traits and immune-capacity traits were detected. The significant QTL for Log-MPS score, located on S. scrofa chromosome 2, could explain 87% of the genetic variance of this score in this analysis. This is the first report of QTL associated with respiratory disease lesions.


Asunto(s)
Resistencia a la Enfermedad/genética , Neumonía Porcina por Mycoplasma/genética , Sitios de Carácter Cuantitativo , Enfermedades Respiratorias/veterinaria , Rinitis Atrófica/veterinaria , Enfermedades de los Porcinos/genética , Animales , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Masculino , Carne , Repeticiones de Microsatélite/genética , Neumonía Porcina por Mycoplasma/inmunología , Enfermedades Respiratorias/genética , Enfermedades Respiratorias/inmunología , Rinitis Atrófica/genética , Rinitis Atrófica/inmunología , Porcinos , Enfermedades de los Porcinos/inmunología
9.
Water Sci Technol ; 63(5): 964-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21411947

RESUMEN

Anaerobic ammonium oxidation (anammox) involves the microbiological oxidation of ammonium with nitrite as the electron acceptor and dinitrogen gas as the main product. The Scalindua species, an anammox genus that dominates natural habitats, plays an important role in catalysing the loss of nitrogen from marine environments. Until now, a few Scalindua species have been reported to be enriched from sea sediments. The objective of this study is to enrich marine anammox bacteria with coastal sediments in Hiroshima Bay as the inocula. The enrichment was achieved using a continuous upflow column reactor with synthetic sea water containing ammonium and nitrite. After 48 days of incubation, a simultaneous decrease in ammonium and nitrite was observed. A total nitrogen removal rate of 1.16 kg-N m(-3) day(-1) was attained after 306 days of incubation when the nitrogen loading rate was 1.32 kg-N m(-3) day(-1). Phylogenetic analysis revealed that the sequence similarity between the marine anammox-like bacteria in this reactor and the unidentified Candidatus Scalindua sp. was 96-98%. We successfully enriched marine anammox bacteria in the sediments of Hiroshima Bay by using synthetic sea water. Further studies are needed to investigate the characteristics of marine anammox bacteria, including optimal pH, temperature, and nitrogen loading rate.


Asunto(s)
Bacterias Anaerobias/metabolismo , Sedimentos Geológicos/microbiología , Compuestos de Amonio Cuaternario/metabolismo , Bacterias Anaerobias/genética , Hibridación Fluorescente in Situ , Japón , Océanos y Mares , Oxidación-Reducción , Filogenia , Compuestos de Amonio Cuaternario/química
10.
J Anim Sci ; 88(1): 23-31, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19749013

RESUMEN

In the livestock industry, meat color has become important because consumer acceptance is subject to the appearance of the product in the marketplace. Our previous analyses of a whole genome QTL scan for various meat qualities using 2 F(2) families from Japanese wild boar (known as a red meat) x Large White and from Duroc x Chinese Jinhua suggested that a meat color (heme content) QTL is located on SSC6. The objective of this study was to fine-map this SSC6 meat color QTL and subsequently investigate positional candidate genes for polymorphisms that may cause changes in meat color. Therefore, we conducted interval mapping on SSC6 using an additional 9 gene markers through combined analyses of the 2 F(2) families of Japanese wild boar x Large White (353 progeny) and Duroc x Chinese Jinhua (204 progeny). Comparative analysis with humans, mice, and cattle suggested that there were 10 functional genes in the region. Among these genes, we suggested that a novel pig gene encoding a nudix (nucleoside diphosphate linked moiety X)-type motif 7 (NUDT7, a member of the nudix hydrolases) is a strong candidate for the QTL because the mouse Nudt7 is reported to hydrolyze succinyl-CoA, a substrate of the reaction limiting the rate of heme biosynthesis. We therefore determined the pig NUDT7 gene sequence including the 5' promoter region and explored genetic polymorphisms between Japanese wild boar and Large White. We identified 116 polymorphisms within the NUDT7 CDS or in the 5' region. None of the AA substitutions were associated with the meat color QTL; however, 3 polymorphisms were found in putative transcription factor recognition sites. We then investigated the differential expression of NUDT7 in Japanese wild boar and Large White by allele-specific quantitative real-time PCR. The expression level of the Large White type allele was greater than that of the Japanese wild-boar-type allele. Consequently, we speculated that the difference in meat color between Japanese wild boar and Large White is caused partly by differential expression of this candidate gene. Upregulation of NUDT7 expression in muscle may reduce succinyl-CoA content and thus reduce the level of heme biosynthesis.


Asunto(s)
Carne/normas , Pirofosfatasas/genética , Sitios de Carácter Cuantitativo , Animales , Mapeo Cromosómico , Clonación Molecular , Regulación Enzimológica de la Expresión Génica , Hemina/metabolismo , Músculo Esquelético/enzimología , Linaje , Reacción en Cadena de la Polimerasa/veterinaria , Pirofosfatasas/metabolismo , Porcinos , Hidrolasas Nudix
11.
Anim Genet ; 41(2): 113-21, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19793267

RESUMEN

Herein, we report the variability among 57 porcine homologs of murine coat colour-related genes. We identified single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) within 44 expressed gene sequences by aligning eight pig complementary DNA (cDNA) samples. The sequence alignment revealed a total of 485 SNPs and 15 InDels. The polymorphisms were then validated by performing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with reference DNA samples obtained from 384 porcine individuals. Of the 384 individuals, three parents of the experimental F(2) family were included to detect polymorphisms between them for linkage mapping. We also genotyped previously reported polymorphisms of 12 genes, and one SNP each in three genes that were detected by performing a BLAST search of the Trace database. A total of 211 SNPs and three InDels were successfully genotyped from our porcine DNA panel. We detected SNPs in 33 of the 44 genes among the parents of an experimental F(2) family and then constructed a linkage map of the 33 genes for this family. The linkage assignment of each gene to the porcine chromosomes was consistent with the location of the BAC clone in the porcine genome and the corresponding gene sequence. We confirmed complete substitutions of EDNRB and MLPH in the Jinhua and Clawn miniature breeds, respectively. Furthermore, we identified polymorphic alleles exclusive to each pig group: 13 for Jinhua, two for Duroc, three for Meishan, four for the Japanese wild boar, one for the Clawn miniature pig and four for the Potbelly pig.


Asunto(s)
Color del Cabello/genética , Polimorfismo Genético , Porcinos/genética , Animales , Mapeo Cromosómico , Mutación INDEL , Ratones , Polimorfismo de Nucleótido Simple , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
12.
Diabetologia ; 52(12): 2513-21, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19812988

RESUMEN

AIM/HYPOTHESIS: We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive. METHODS: We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA. RESULTS: DRB1*0405-DQB1*0401, DRB1*0802-DQB1*0302 and DRB1*0901-DQB1*0303 were associated with acute-onset type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 genotype achieving the highest odds ratio of 42.7. DRB1*1501-DQB1*0602 and DRB1*1502-DQB1*0601 were negatively associated with acute-onset type 1 diabetes. A similar tendency was observed for slowly progressive type 1 diabetes. In contrast, only DRB1*0405-DQB1*0401 was associated with fulminant type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0405-DQB1*0401 genotype showing the highest odds ratio of 11.2. DRB1*0802-DQB1*0302, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 and DRB1*1501-DQB1*0602 were not associated with fulminant type 1 diabetes. The association of class I alleles and a panel of SNPs in an extended HLA region with fulminant type 1 diabetes was also different from that seen for the acute-onset and slowly progressive forms. The presence of both one and two susceptible haplotypes conferred susceptibility to slowly progressive type 1 diabetes, whereas the presence of two susceptible haplotypes was required to confer susceptibility to acute-onset and fulminant type 1 diabetes. CONCLUSIONS/INTERPRETATION: These data suggest that HLA associations with fulminant type 1 diabetes are qualitatively different from those with other subtypes of type 1 diabetes, whereas the HLA contribution to slowly progressive type 1 diabetes is qualitatively similar to, but quantitatively different from, that in acute-onset type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Antígenos HLA/genética , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/prevención & control , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Intrones/genética , Japón , Regiones Promotoras Genéticas/genética , Valores de Referencia
13.
Anim Genet ; 37(4): 342-7, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16879343

RESUMEN

Here, we analysed quantitative trait loci (QTL) for fatty acid composition, one of the factors affecting fat quality, in a Japanese wild boar x Large White cross. We found 25 significant effects for 17 traits at 13 positions at the 5% genome-wise level, of which 16 effects for 12 traits at 10 positions were significant at the 1% level. QTL for saturated fatty acids (SFA) in back fat were mapped to swine (Sus scrofa) chromosomes (SSC) 1p, 9 and 15. QTL for unsaturated fatty acids in back fat were mapped to SSC1p, 1q, 4, 5, 9, 15 and 17. Using a regression model that fits back fat thickness as a covariate, two of the QTL for linoleic acid content on SSC4 and SSC17 were not significant, but one QTL for total SFA composition was detected on SSC5 with correction for back fat thickness. Wild boar alleles at six of seven QTL tended to increase SFAs and to decrease unsaturated fatty acids. QTL for fatty acid composition in perirenal fat were mapped on SSC2, 3, 4, 5, 6, 14, 16 and X. QTL for melting point (in back fat samples) were mapped on SSC1, 2 and 15. Wild boar alleles in QTL on SSC1 and SSC15 were associated with elevated melting points whereas those on SSC2 were associated with lower melting point measurements.


Asunto(s)
Tejido Adiposo/química , Cruzamientos Genéticos , Ácidos Grasos/química , Sitios de Carácter Cuantitativo , Sus scrofa/genética , Alelos , Animales , Composición Corporal/genética , Cruzamiento , Mapeo Cromosómico , Cromosomas , Ácidos Grasos/análisis , Análisis de Regresión , Temperatura de Transición
14.
Heredity (Edinb) ; 96(2): 185-94, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16391550

RESUMEN

Many traits including shapes and colors of flowers, fruits and seeds in plants, as well as coat colors and some behavioral properties in animals, are recorded in discrete categories. If categories are ordered, genetic analyses of the categorical traits are often performed using the threshold model, which considers a latent continuous variable, called the liability, underlying a trait and assumes the monotonic relationship between the phenotype and the liability. In some categorical traits, however, descriptions of phenotypes are purely nominal and the phenotypic scores cannot be ordered. The threshold model is unreasonable for the analyses of such unordered categorical traits. In this study, we developed a method for interval mapping of loci affecting unordered categorical traits with more than two categories. The probability of the phenotype of an individual falling in each of the categories was expressed by a polychotomous logistic model, in which the log-odds for each category relative to the reference category were assumed to follow a linear model including genotype at a locus affecting a trait as covariate. Based on the model, the interval mapping using a maximum likelihood method was devised for the analysis of complex categorical traits described with unordered categories. We confined ourselves to the case of F2 populations derived from a cross between two inbred lines, although this approach can easily be extended to the analyses for other populations of general structures. As results of analyses of simulated data show, the method showed high efficiency in detecting the loci affecting unordered categorical traits.


Asunto(s)
Ligamiento Genético , Modelos Genéticos , Sitios de Carácter Cuantitativo , Animales , Simulación por Computador , Funciones de Verosimilitud
15.
Anim Genet ; 37(1): 10-6, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16441290

RESUMEN

To clarify the structure of the porcine genomic region that contains quantitative trait loci (QTL) related to fat, we constructed a bacterial artificial chromosome (BAC) contig of the region from DST to SRPK1 on porcine chromosome 7 and performed low-redundancy 'skim' shotgun sequencing of the clones that composed a minimum tiling path of the contig. This analysis revealed that the gene order from VPS52 to SRPK1 is conserved between human and swine and that comparison with the human sequence identified a rearrangement in the swine genome at the proximal end of VPS52. Analysis of the nucleotide sequences of three BAC clones that included the rearrangement point demonstrated that COL21A1 and DST, which were not present in the corresponding human region, were located adjacent to the rearrangement point. These results provide useful information about the genomic region containing QTL for fat in pigs and help to clarify the structure of the so-called 'extended-class II' region distal to the porcine major histocompatibility complex class II region.


Asunto(s)
Cromosomas de los Mamíferos/genética , Orden Génico/genética , Genoma/genética , Porcinos/genética , Tejido Adiposo , Animales , Secuencia de Bases , Cromosomas Artificiales Bacterianos , Secuencia Conservada/genética , Genes MHC Clase II/genética , Humanos , Hibridación Fluorescente in Situ , Datos de Secuencia Molecular , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ADN
18.
J Anim Sci ; 83(10): 2247-54, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16160033

RESUMEN

The objective of the research was to identify QTL affecting the number of vertebrae in swine, one of the major determining factors of growth and body composition. Previously, we reported a QTL for the number of vertebrae located on SSC1qter (terminal band of the q arm of SSC 1) in an F2 family produced by crossing a Göttingen miniature male with two Meishan females. Eight other swine families were subsequently produced by crosses between different breeds of European, Asian, and miniature pigs. In these families, the QTL on SSC1qter for the number of vertebrae was detected. Unlike the Asian alleles, all European alleles in this study had the effect of increasing the number of vertebrae by 0.44 to 0.69 and acted additively without dominance. The Göttingen miniature sire, for which we previously reported a smaller additive effect, seemed to be heterozygous at the QTL. In the present study, another QTL was found for the number of vertebrae on SSC7. This QTL was not fixed in the European pigs used as parents in our experimental families, and some of the European alleles increased the number of vertebrae. A half-sib analysis confirmed that this QTL was segregating in a commercial Large White population. Analysis in an F2 family in which the parental pigs were fixed for alternative alleles revealed that the effects of the QTL on SSC1 and on SSC7 were additive and similar in size. The two QTL acted independently without epistatic effects and explained an increase of more than two vertebrae.


Asunto(s)
Mapeo Cromosómico/veterinaria , Sitios de Carácter Cuantitativo/fisiología , Columna Vertebral/fisiología , Sus scrofa/genética , Animales , Cromosomas/genética , Femenino , Heterocigoto , Endogamia , Masculino , Sitios de Carácter Cuantitativo/genética , Columna Vertebral/anatomía & histología , Sus scrofa/anatomía & histología , Sus scrofa/fisiología
19.
Heredity (Edinb) ; 94(3): 326-37, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15674384

RESUMEN

In this paper, we propose a new Bayesian method for QTL analysis in outbred F2 families based on Markov chain Monte Carlo (MCMC) estimation allowing inference about whether each of F0 founders (grandparents) is homozygous or heterozygous at QTL. This, in turn, allows us to select a model accurately explaining observations of phenotypes for F2 individuals. The proposed method performs the fitting a statistical model of the two possible QTL states in each F0 grandparent, that is, homozygous and heterozygous at QTL, and gives a posterior distribution for the QTL states in each F0 grandparent. We confine ourselves to the discrimination of two QTL states, homozygous or heterozygous, for each of the F0 grandparents without taking into consideration whether common alleles are shared by F0 grandparents. The statistical model includes allelic effects and dominance effects for each QTL. The number of parameters representing allelic effects and dominance effects is therefore changed depending on the QTL states. A Reversible Jump MCMC technique is used for transition between the models of different dimensions. The effectiveness of the proposed method was investigated using simulation experiments. It was practicable to estimate the QTL states of F0 grandparents as well as the number, the locations and the effects of QTL segregating in an outbred F2 family.


Asunto(s)
Animales no Consanguíneos/genética , Teorema de Bayes , Sitios de Carácter Cuantitativo/genética , Alelos , Animales , Genotipo , Humanos , Cadenas de Markov , Linaje
20.
J Anim Sci ; 83(2): 308-15, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15644501

RESUMEN

Three generations of a swine family produced by crossing a Japanese wild boar and three Large White female pigs were used to map QTL for various production traits. Here we report the results of QTL analyses for skeletal muscle fiber composition and meat quality traits based on phenotypic data of 353 F(2) animals and genotypic data of 225 markers covering almost the entire pig genome for all of the F(2) animals as well as their F(1) parents and F(0) grandparents. The results of a genome scan using least squares regression interval mapping provided evidence that QTL (<1% genome-wise error rate) affected the proportion of the number of type IIA muscle fibers on SSC2, the number of type IIB on SSC14, the relative area (RA) of type I on SSCX, the RA of type IIA on SSC6, the RA of type IIB on SSC6 and SSC14, the Minolta a* values of loin on SSC4 and SSC6, the Minolta b* value of loin on SSC15, and the hematin content of the LM on SSC6. Quantitative trait loci (<5% genome-wise error rate) were found for the number of type I on SSC1, SSC14, and SSCX, for the number of type IIA on SSC14, for the number of type IIB on SSC2, for the RA of type IIA on SSC2, for the Minolta b* value of loin on SSC3, for the pH of loin on SSC15, and for the i.m. fat content on SSC15. Twenty-four QTL were detected for 11 traits at the 5% genome-wise level. Some traits were associated with each other, so the 24 QTL were located on 11 genomic regions. In five QTL located on SSC2, SSC6, and SSC14, each wild boar allele had the effect of increasing types I and IIA muscle fibers and decreasing type IIB muscle fibers. These effects are expected to improve meat quality.


Asunto(s)
Mapeo Cromosómico/veterinaria , Carne/normas , Músculo Esquelético/fisiología , Sitios de Carácter Cuantitativo , Sus scrofa/fisiología , Animales , Cruzamiento , Cartilla de ADN/química , Femenino , Japón , Análisis de los Mínimos Cuadrados , Masculino , Repeticiones de Microsatélite/genética , Repeticiones de Microsatélite/fisiología , Modelos Estadísticos , Fibras Musculares Esqueléticas/fisiología , Sitios de Carácter Cuantitativo/fisiología , Sus scrofa/genética
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